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The role of ZYG11B, a CUL2-complex-associated E3 ubiquitin ligase from the Zyg-11 family, in antiviral defense against EV71 remains unclear. To our knowledge, this study is the first to reveal that ZYG11B targets EV71 VP1 for proteasomal degradation via the ubiquitin-proteasome pathway, with CRL2\n              <jats:sup>ZYG11B<\/jats:sup>\n              complex activity specifically driving K33-linked ubiquitination. Mass spectrometry and immunoprecipitation analyses confirmed the interaction between ZYG11B and VP1 and identified key domains required for binding both VP1 and CUL2. Comparative analyses showed that VP1 ubiquitination sites are highly conserved across related enteroviruses, including CA6, CA16, and EVD68. Functional assays further demonstrated that ZYG11B restricts these viruses, highlighting its potential as a broad-spectrum antiviral target. These findings establish ZYG11B as a critical effector in host antiviral responses and support its therapeutic potential for managing enterovirus infections.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              E3 ubiquitin ligases and deubiquitinases have become important topics of competition between viruses and hosts. Here, we identified CRL2\n              <jats:sup>ZYG11B<\/jats:sup>\n              as an E3 ubiquitin ligase complex capable of degrading structural protein VP1 of enteroviruses, making ZYG11B a broad-spectrum antiviral factor. We first proposed the inhibitory effect of ZYG11B on viruses and identified the structural domains of ZYG11B connecting substrates and CUL2, providing new targets for the design of antiviral drugs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00030-25","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T14:42:48Z","timestamp":1743000168000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["ZYG11B suppresses multiple enteroviruses by triggering viral VP1 degradation"],"prefix":"10.1128","volume":"99","author":[{"given":"Li","family":"Tian","sequence":"first","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhong","family":"Mi","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijing","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulong","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-521X","authenticated-orcid":true,"given":"Wenyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]},{"name":"Department of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3795-7220","authenticated-orcid":false,"given":"Zhaolong","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Virology and AIDS Research, the First Hospital of Jilin University","place":["Changchun, China"]},{"name":"Department of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.47102\/annals-acadmedsg.V38N2p106"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70194-8"},{"key":"e_1_3_4_4_2","first-page":"261","article-title":"An unusual presentation of gluteal hematoma during anticoagulation therapy for deep venous thrombosis in spinal cord injury","volume":"67","author":"Balmaseda MT","year":"1988","unstructured":"Balmaseda MT, Gordon C, Burke M, Michael R. 1988. 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